The biological interactions between Pb and Ca are complex and not well- understoon, but can be demonstrated in virtually every tissue. High affinity lead-binding to intracellular calcium receptor and transport proteins as well as the involvement of lead in calcium-activated and calcium-regulating processes may provide a molecular basis for the broad spectrum cellar and systemic effects. The intestinal absorptive cells are responsible for transporting the entire body complement of calcium and most of the body lead burden. They represent, therefore, the first critical step in maintaining systemic and cellular homeostasis, as well as the first line of the defense against lead poisoning. Any interactions which occur at this level, either to enhance the body burden of Pb or to diminish the transport of calcium, may have serious health-related repercussions. The objectives of the proposed studies are; to detail those interactions involving calcium, lead, phosphorus and the vitamin D endocrine system which ultimately influence intestinal function and calcium homeostasis, and; to critically examine the intestinal transport pathways for calcium and lead. Experiments will be conducted to compare the effects of the vitamin D endocrine system on intestinal calcium and lead transport and body lead burden with special emphasis on lead intoxication. Similarly, the effects of dietary lead, calcium and phosphorus status and body lead burden on vitamin D endocrine system function will be examined. A whole animal model system will be employed. Intestinal lead and calcium absorption will be determined by the in situ ligated intestinal techniques. Direct intestinal interactions of lead and calcium will be investigated in addition to systemic interactions. The synthesis and circulating levels of 1,25(OH)2D as well as tibial and renal lead retention will be measured. These studies will be characterized by temporal comparisons of all variables and response elements to provide an integrated view of these complex interactions. Additional studies will focus on elucidating the intestinal transort pathways for lead and calcium as well as the possibility of interactions at specific sites. Ion microscopic and microautoradiographic techniques in combination with an in situ system will be employed to study integrated calcium and lead transport. Radiotracer uptake studies in microvillar and basolateral membrane vesicles will be used to examine specific transport events and the possibility of interactions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES004072-08
Application #
3251950
Study Section
Toxicology Subcommittee 2 (TOX)
Project Start
1986-06-15
Project End
1995-06-30
Budget Start
1993-07-01
Budget End
1994-06-30
Support Year
8
Fiscal Year
1993
Total Cost
Indirect Cost
Name
Cornell University
Department
Type
Schools of Veterinary Medicine
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Fullmer, C S (1997) Lead-calcium interactions: involvement of 1,25-dihydroxyvitamin D. Environ Res 72:45-55
Fullmer, C S; Chandra, S; Smith, C A et al. (1996) Ion microscopic imaging of calcium during 1,25-dihydroxyvitamin D-mediated intestinal absorption. Histochem Cell Biol 106:215-22
Fullmer, C S (1995) Dietary calcium levels and treatment interval determine the effects of lead ingestion on plasma 1,25-dihydroxyvitamin D concentration in chicks. J Nutr 125:1328-33
Wasserman, R H; Fullmer, C S (1995) Vitamin D and intestinal calcium transport: facts, speculations and hypotheses. J Nutr 125:1971S-1979S
Corradino, R A (1993) Calbindin D28K regulation in precociously matured chick egg shell gland in vitro. Gen Comp Endocrinol 91:158-66
de Talamoni, N; Smith, C A; Wasserman, R H et al. (1993) Immunocytochemical localization of the plasma membrane calcium pump, calbindin-D28k, and parvalbumin in Purkinje cells of avian and mammalian cerebellum. Proc Natl Acad Sci U S A 90:11949-53
Corradino, R A; Smith, C A; Krook, L P et al. (1993) Tissue-specific regulation of shell gland calbindin D28K biosynthesis by estradiol in precociously matured, vitamin D-depleted chicks. Endocrinology 132:193-8
Brouwer, M; Brouwer-Hoexum, T (1992) Glutathione-mediated transfer of copper(I) into American lobster apohemocyanin. Biochemistry 31:4096-102
Fullmer, C S (1992) Intestinal calcium absorption: calcium entry. J Nutr 122:644-50
Fullmer, C S (1992) Intestinal interactions of lead and calcium. Neurotoxicology 13:799-807

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